specific HLA-E restricted T cells are induced during infection but not after BCG administration in non-human primates and humans.
Linda Voogd, Marjolein van Wolfswinkel, Iman Satti, Andrew D White, Karin Dijkman, Anele Gela, Krista E van Meijgaarden, Kees L M C Franken, Julia L Marshall, Tom H M Ottenhoff, Thomas J Scriba, Helen McShane, Sally A Sharpe, Frank A W Verreck, Simone A Joosten
Author Information
Linda Voogd: Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. ORCID
Marjolein van Wolfswinkel: Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Iman Satti: The Jenner Institute, University of Oxford, Oxford, United Kingdom (UK).
Andrew D White: UK Health Security Agency, Porton Down, UK.
Karin Dijkman: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Anele Gela: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Krista E van Meijgaarden: Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Kees L M C Franken: Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Julia L Marshall: The Jenner Institute, University of Oxford, Oxford, United Kingdom (UK).
Tom H M Ottenhoff: Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Thomas J Scriba: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa. ORCID
Helen McShane: The Jenner Institute, University of Oxford, Oxford, United Kingdom (UK).
Sally A Sharpe: UK Health Security Agency, Porton Down, UK.
Frank A W Verreck: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Simone A Joosten: Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Novel vaccines targeting the world's deadliest pathogen () are urgently needed as the efficacy of the Bacillus Calmette-Gu��rin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule and HLA-E restricted specific CD8 T cells can control intracellular growth, making HLA-E a promising vaccine target for . In this study, we evaluated the frequency and phenotype of HLA-E restricted specific CD4/CD8 T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. BCG vaccination followed by challenge in NHPs did not affect the frequency of circulating and local HLA-E/ CD4 and CD8 T cells, and we saw the same in humans receiving BCG. HLA-E/ T cell frequencies were significantly increased after challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Together, HLA-E/ restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.
